Antibodies from patients with gliomas were shown by immune precipitation to react with several different proteins in the glioma cell membrane. There, likewise, seemed to be a biologic dichotomy of these antigens, since cytotoxic IgG reacted with a 63,000 dalton protein. We propose to use immune precipitation or affinity chromatography, in combination with an electrophoretic or chromatographic technique, to isolate the individual antigens in small amounts, in order, in turn, to raise antigen-specific hyperimmune antisera. The specific antisera will be used to enumerate the individual determinants by quantitative binding studies and to study the interrelationships of the various surface antigens by binding inhibition, co-capping and sequential immune precipitation. The antisera will also be used to assess the effects of primary immune reactivity against specific determinants on the functional integrity of the cell, as measured by generation time and enzymatic and bioelectric activity of the membrane. It is hoped that such studies will help clarify the reasons for the heterogeneity of the immune response to a tumor and some of the mechanisms of immunological effects on the tumor. The ultimate goal is to manipulate, to the host's advantage, the various components of the tumor-directed immune response. We have established a syngeneic murine tumor system that shows an antigenic dichotomy analogous to that seen with human gliomas. We will try to control the composite immune response to the tumor by manipulating the immune response to the individual determinants of the tumor.